Staphylococcus aureus SufT: an essential iron‐sulphur cluster assembly factor in cells experiencing a high‐demand for lipoic acid

Summary Staphylococcus aureus SufT is composed solely of the domain of unknown function 59 (DUF59) and has a role in the maturation of iron‐sulphur (Fe‐S) proteins. We report that SufT is essential for S. aureus when growth is heavily reliant upon lipoamide‐utilizing enzymes, but dispensable when this reliance is decreased. LipA requires Fe‐S clusters for lipoic acid (LA) synthesis and a ΔsufT strain had phenotypes suggestive of decreased LA production and decreased activities of lipoamide‐requiring enzymes. Fermentative growth, a null clpC allele, or decreased flux through the TCA cycle diminished the demand for LA and rendered SufT non‐essential. Abundance of the Fe‐S cluster carrier Nfu was increased in a ΔclpC strain and a null clpC allele was unable to suppress the LA requirement of a ΔsufT Δnfu strain. Over‐expression of nfu suppressed the LA requirement of the ΔsufT strain. We propose a model wherein SufT, and by extension the DUF59, is essential for the maturation of holo‐LipA in S. aureus cells experiencing a high demand for lipoamide‐dependent enzymes. The findings presented suggest that the demand for products of Fe‐S enzymes is a factor governing the usage of one Fe‐S cluster assembly factor over another in the maturation of apo‐proteins. Cells contain iron‐sulphur (Fe‐S) cluster utilizing proteins and proteins that facilitate cluster assembly. Lipoic acid (LA) is a product of the Fe‐S cluster dependent enzyme LipA. The SufT Fe‐S cluster assembly factor is essential in cells experiencing a high demand for lipoamide‐dependent enzymes. We propose that the demand for products of Fe‐S enzymes is a factor governing the usage of one Fe‐S assembly factor over another in the maturation of apo‐proteins.